scholarly journals Designing a Genetic Screen to Identify Factors Required for Meiotic Nuclear Rejuvenation

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 973-973
Author(s):  
Chelsey Jones

Abstract During the natural cycle of life, most eukaryotic organisms grow old, age, and die. A common natural mechanism by which organisms “reset” their lifespan is through sexual reproduction; however, how this rejuvenation takes place remains unknown. My lab has found that meiosis in budding yeast, the developmental program that forms sex cells, eliminates age-induced damage. This involves the formation of a novel nuclear compartment, the Gametogenesis Uninherited Nuclear Compartment (GUNC), which acts as a trash can for accumulated age-induced damage. To understand the molecular details of this process, I worked on designing a screen for genes involved in GUNC formation. My mentor and I fused three different proteins targeted to the GUNC and a protein that is able to bind to a drug-resistance plasmid, in order to couple the inheritance of a selectable DNA marker with the elimination of age-induced damage. Initial testing of these three fusion proteins suggested that they were unable to successfully target the plasmid to the GUNC; as such, testing of additional candidate proteins is necessary. We plan to eventually use this system to identify mutations that disrupt GUNC formation and cause inheritance of the drug-resistance plasmid. By identifying and perturbing proteins involved in GUNC formation, we are hoping to be able to drive the inheritance of specific types of age-induced damage, allowing for the determination of what a symptom versus a cause of aging is.

2020 ◽  
Vol 17 (6) ◽  
pp. 397-407
Author(s):  
Maryam Jarchi ◽  
Farah Bokharaei-Salim ◽  
Maryam Esghaei ◽  
Seyed Jalal Kiani ◽  
Fatemeh Jahanbakhsh ◽  
...  

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated. Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.


Intervirology ◽  
2014 ◽  
Vol 57 (5) ◽  
pp. 297-299 ◽  
Author(s):  
Özlem Yoldaş ◽  
Ali Ağaçfidan ◽  
Nadine Lübke ◽  
Ayper Somer ◽  
Selda Hançerli ◽  
...  

1989 ◽  
Vol 9 (11) ◽  
pp. 4746-4749 ◽  
Author(s):  
D I Chasman ◽  
J Leatherwood ◽  
M Carey ◽  
M Ptashne ◽  
R D Kornberg

Fusion proteins known to activate transcription in vivo were tested for the ability to stimulate transcription in vitro in a recently developed Saccharomyces cerevisiae RNA polymerase II transcription system. One fusion protein, whose activation domain was derived from the herpesvirus transcriptional activator VP16, gave more than 100-fold stimulation in the in vitro system. The order of effects of the various proteins was the same for transcription in vitro and in vivo, suggesting that the natural mechanism of activation is preserved in vitro.


2021 ◽  
Vol 9 (3) ◽  
pp. 5-10
Author(s):  
N.V. Kuznetsov ◽  
A.S. Lesonen ◽  
U.M. Markelov ◽  
E.D. Mikhailova

The article presents the results of predicting the dynamics of the spread of new cases of tuberculosis (TB) with multiple drug resistance (MDR) in the Republic of Karelia, as well as the costs of treating patients with tuberculosis, considering the different effectiveness of treatment. It has been demonstrated that while enhancing efficiency of treatment, due to the rapid determination of drug resistance by the method of polymerase chain reaction and a decrease in treatment gaps (using food kits), the effectiveness of treatment is significantly increased and the prevalence of MDR-TB decreases, which leads to significant budget savings.


2005 ◽  
Vol 52 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Agata Czyz ◽  
Grzegorz Wegrzyn

Members of the Obg subfamily of small GTP-binding proteins (called Obg, CgtA, ObgE or YhbZ in different bacterial species) have been found in various prokaryotic and eukaryotic organisms, ranging from bacteria to humans. Although serious changes in phenotypes are observed in mutant bacteria devoid of Obg or its homologues, specific roles of these GTP-binding proteins remain largely unknown. Recent genetic and biochemical studies, as well as determination of the structures of Obg proteins from Bacillus subtilis and Thermus thermophilus, shed new light on the possible functions of the members of the Obg subfamily and may constitute a starting point for the elucidation of their exact biological role.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Małgorzata Olejnik ◽  
Piotr Jedziniak ◽  
Teresa Szprengier-Juszkiewicz

The control of levels of anticoccidial feed additives in targeted feeds plays an important role in the assurance of efficiency of animal treatment, prevention of drug resistance, and food safety. The robust and labour-efficient method for the simultaneous determination of six ionophore coccidiostats (lasalocid, maduramicin, monensin, narasin, salinomycin, and semduramicin) in targeted feed has been developed. Properly grinded and homogenized feed sample was spiked with internal standard (monesin methyl ester) and extracted with methanol. The extract was analysed with reversed phase HPLC without any further purification. The separation of the analytes with conventional C18 and core-shell columns was compared. Lasalocid was analysed with fluorescence detection, whereas other ionophores were detected with UV-Vis detector after derivatisation with vanillin in the presence of sulfuric acid. Fortified samples and targeted feeds at authorized levels were used for method validation. Recovery was in the range of 85–110%, depending on the analyte. The within-laboratory reproducibility did not exceed the target value from Horwitz equation. The results of the proficiency tests (z-scores in the range of −1.0 to 1.9) confirmed the reliability of the developed protocol.


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